This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background. The prevalence and incidence of insulin resistance and type 2 diabetes (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. Objective. We evaluated whether the peroxisome proliferator activated receptor-gamma agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV infected adults with insulin resistance and central adiposity. Design. Forty-four HIV infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4-months of pioglitazone (30mg/d) with or without supervised, progressive aerobic and resistance exercise training (11/2 -2 hr/d, 3 days/wk). The hyperinsulinemic-euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity.